Effect of Depression and Anxiety on Cognition in Parkinson’s Disease

It is important to pay attention to adverse effects and overlapping symptoms when treating depression or anxiety in Parkinson's.

Although motor symptoms are the hallmark feature of Parkinson’s disease (PD), nonmotor symptoms contribute significantly to the disability and reduced quality of life that patients with PD often experience. Among these, neuropsychiatric symptoms such as depression and anxiety are common, and they are often undiagnosed and untreated in this population. This oversight can lead to worse overall outcomes in the course of the disease.

According to recent findings, rates of major depressive disorder and anxiety disorders in patients with PD are 17%1 and 31%,2 respectively, and the 2 disorders can co-occur. An even greater percentage of patients have clinically significant depressive symptoms regardless of whether they have been formally diagnosed with major depressive disorder. “In addition to dopamine deficiency, [PD] can also cause reductions in serotonin, norepinephrine, and acetylcholine levels in the brain,” said Pinky Agarwal, MD, a neurologist at EvergreenHealth in Kirkland, Washington. “This can lead to depression, even several years before the onset of motor symptoms; hence, depression is not just reactive to the diagnosis of [PD],” she told Neurology Advisor.

The effects of psychological symptoms are not limited to mood impairment. “Not only can these symptoms exacerbate motor symptoms, they can interfere with cognition and even increase the risk of dementia,” and they have been shown to contribute to more rapid cognitive decline, according to Julie A. Fields, PhD, LP, a neuropsychologist and associate professor of psychology at the Mayo Clinic College of Medicine, Rochester, Minnesota.3 A recent study of 185 patients newly diagnosed with PD, for example, found that the odds of having cognitive impairment were 3-fold in those with anxiety vs in those without anxiety.4

Executive functions are particularly vulnerable to depression, anxiety, and apathy, including attention shifting, cognitive flexibility, planning, reasoning, and problem-solving. Further compounding the clinical picture, several symptoms of mental disorders and PD overlap. One such symptom is bradyphrenia, a common cognitive feature of PD also seen in mood disorders that adds to learning and memory deficits. “Problems with slowed processing, executive functioning, learning, and memory lead to increased functional decline and debility over and above that associated with motor dysfunction,” Dr Fields told Neurology Advisor.

The independent and combined effects of the psychological and cognitive symptoms and their subsequent effect on other realms of patient functioning may compound PD outcomes in several ways. In addition to the pathophysiological effects of depression, for instance, patients with PD and depression “typically have reduced social interaction and efforts to keep themselves physically and mentally active, which can accelerate cognitive decline,” said Dr Agarwal.

Identification and Treatment

Although treating comorbid neuropsychiatric disorders can significantly improve motor symptoms and cognition in these patients, identifying these conditions in PD can be difficult because of the overlapping effects of the different types of symptoms. Assessment of mood should be a standard part of the evaluation, Dr Fields advises. Simply asking about anxiety and depression can lead to early identification, said Dr Agarwal, who notes that depression in PD tends to be slightly different from typical depression and is characterized by more pessimism, less self-blame, and less suicidal behavior.

Because apathy can mimic depression in patients with PD, it is important to question the patient “rather than just relying on family members to assess for depression, since facial masking, soft speech, and slow movements may appear like depression to them,” according to Dr Agarwal. It can be helpful to ask patients if they feel sad and whether they no longer experience pleasure from activities they previously enjoyed. “Once it has been clarified that the patient has depression and not just apathy, it should be treated; untreated depression can mimic dementia.”

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She points out that amitriptyline, although typically helpful in treating depression, can worsen cognition in patients with PD through its anticholinergic effects. Selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and mirtazapine may be helpful in treating depression and anxiety without these adverse effects. Dosing in the middle to low range is typically appropriate, as these agents can worsen tremor in patients with PD, she explained. They can also increase the risk for serotonin syndrome if used concurrently with monoamine oxidase-B inhibitors such as selegiline or rasagiline. In some cases, dopamine agonists can help with motor symptoms, as well as with depression.

“Paradoxically, side effects of psychotropic medications used to treat mood can include impaired cognition, particularly attention and memory, as well as sedation or insomnia and increased motor symptoms, so risks and benefits should be fully explored in the context of existing motor and nonmotor symptoms,” said Dr Fields. Similarly, certain medications used to treat motor symptoms of PD can have the same negative adverse effects as psychotropic medications.

She notes that nonpharmacologic behavioral treatments — including psychotherapy, mindfulness meditation, and exercise — may be as effective as medications for some patients and without the negative adverse effects. A recent review, for example, concluded that aerobic exercise and strength training represent adjunct treatments that can improve mood, sleep, and cognition in PD patients.5

“The degree to which we can control the various motor and nonmotor symptoms and thereby modulate their impact on each other and perhaps alter the course of the disease, or at the very least ameliorate the symptoms, really takes an individualized approach,” Dr Fields emphasized. This should include a thorough assessment to recognize symptoms, track treatment response, and modify treatment as warranted; such as, for example, when the disease progresses or medications lose their efficacy. This requires an interdisciplinary approach that neurologists can help to facilitate, as they are often the first point of contact for patients with PD.

“Every patient’s response to medications, and even nonpharmacologic treatments, is different,” said Dr Fields. “[PD] is not static, and continued communication between patients and care providers is absolutely key in order to achieve the best possible outcomes.”